Differential expression of thioredoxin binding protein-2/Txnip in human placenta: Possible involvement of hypoxia in its suppression during early pregnancy.

Aim: Thioredoxin binding protein-2 (TBP-2), which is identical to thioredoxin interacting protein (Txnip), controls cellular proliferation and differentiation. The aim of the present study was to compare TBP-2 protein and mRNA expression in human placenta during the three trimesters of pregnancy and to investigate the role of hypoxia in the change of these expressions in placental tissue. A secondary objective was to determine the gene expression of peroxisome proliferator-activated receptors (PPARs) in TBP-2 deficient placenta using TBP-2 gene disrupted mice (TBP-2 ).

Methods: Protein and mRNA expression of TBP-2 in human placenta from each trimester were analyzed by immunohistochemistry, Western blots, and by quantitative reverse-transcriptase-polymerase chain reaction. The effect of hypoxia on TBP-2 expression was tested using an explant culture of human placenta. In TBP-2 mouse placenta, we detected PPAR mRNA expression.

Results: TBP-2 was located in syncytiotrophoblasts and cytotrophoblasts, and also in the endothelium in human placenta. Its expression in the placenta was low in the first trimester, and increased in the second and third trimesters. Hypoxia decreased TBP-2 mRNA and protein expression in human placental explant culture. In TBP-2 mice, placental mRNA levels of PPARα and γ were significantly suppressed compared with those in wild-type mice.

Conclusion: Hypoxia suppresses TBP-2 gene expression, which may ultimately alter placental development.